Real-world treatment patterns and use of adjunctive pain and anti-inflammatory medications among patients with psoriatic arthritis treated with IL-17A inhibitors in the United States

BACKGROUND: Much of the current research on treatment patterns and use of adjunctive pain and anti-inflammatory medications among patients living with psoriatic arthritis (PsA) predates the approval and uptake of IL (interleukin)-17A inhibitors. OBJECTIVES: To compare real-world treatment patterns and use of adjunctive pain and antiinflammatory medications between patients with PsA initiating the IL-17A inhibitors, ixekizumab and secukinumab, in a US-managed care population. METHODS: We conducted a retrospective cohort study using the HealthCore Integrated Research Database. Patients with a PsA diagnosis who initiated ixekizumab or secukinumab treatment between December 1, 2017, and November 30, 2019, were identified. Two cohorts were created based on which of the 2 medications was initiated (index date), and patients with prior use of either drug were excluded, as were patients with ankylosing spondylitis. Patients had to be continuously enrolled in the health plan for 6 months prior to (baseline) and 12 months after the index date (post-index). Inverse probability of treatment weighting was used to minimize confounding from baseline demographic and clinical differences between cohorts. Treatment patterns (dosing, persistence, discontinuation, and switching) and use of adjunctive pain/anti-inflammatory medications were assessed and compared between weighted cohorts using chi-square and t-tests. RESULTS: In total, 407 patients were identified in the ixekizumab cohort (mean age 51.6 years; 54% female) and 1,508 patients were identified in the secukinumab cohort (mean age 50.1 years; 59% female). Prior to weighting, presence of a psoriasis diagnosis code (ixekizumab: 60% vs secukinumab: 45%; standardized difference [std diff] = −0.30), specialty of the index prescriber (std diff = 0.38), and mean number of prior advanced therapies (2.0 vs 1.5; std diff = −0.33) were different between cohorts. Cohorts were well balanced after weighting. The majority of secukinumab patients (71%) received an index dose of 300 mg. Rates of persistence (ixekizumab: 40% vs secukinumab: 43%; P = 0.411) and switching (25% vs 20%; P = 0.072) were not statistically different between cohorts. Use of new adjunctive pain and anti-inflammatory medications was not statistically different between cohorts either (ixekizumab: 63% vs secukinumab: 58%; P = 0.187). CONCLUSIONS: Real-world treatment patterns and use of adjunctive pain and anti-inflammatory medications were similar in patients with PsA initiating ixekizumab and secukinumab in this US-managed care population. Further research examining reasons for discontinuation, switching, and use of adjunctive medications may help inform treatment decisions for patients living with PsA.

care population.

METHODS:
We conducted a retrospective cohort study using the HealthCore Integrated Research Database. Patients with a PsA diagnosis who initiated ixekizumab or secukinumab treatment between December 1, 2017, and November 30, 2019, were identified. Two cohorts were created based on which of the 2 medications was initiated (index date), and patients with prior use of either drug were excluded, as were patients with ankylosing spondylitis. Patients had to be continuously enrolled in the health plan for 6 months prior to (baseline) and 12 months after the index date (post-index). Inverse probability of treatment weighting was used to minimize confounding from baseline demographic and clinical differences between cohorts. Treatment patterns (dosing, persistence, discontinuation, and switching) and use of adjunctive pain/antiinflammatory medications were assessed and compared between weighted cohorts using chi-square and t-tests.

Plain language summary
Patients with psoriatic arthritis may take the medications ixekizumab (Taltz) or secukinumab (Cosentyx) to treat their symptoms. We used information from health insurance claims in the United States to see if there are differences in how long patients use either medication or differences in whether they need additional medications to reduce their symptoms. We found that patients had similar experiences on both medications.

Implications for managed care pharmacy
This study examines 1-year treatment patterns (dosing, persistence, discontinuation, and switching) and use of pain and anti-inflammatory medications between patients in the United States with psoriatic arthritis initiating ixekizumab vs secukinumab. Study results found that patients initiating ixekizumab and secukinumab had similar treatment patterns and use of adjunctive pain and anti-inflammatory medications. This research may inform both formulary development and clinical programs as it directly compares real-world outcomes of 2 interleukin-17A inhibitors.
Psoriatic arthritis (PsA), a chronic, immune-mediated, inflammatory condition, affects the joints and connective tissue leading to pain, stiffness, and swelling. 1 In the United States, approximately 0.06% to 0.25% of the population is living with PsA, and between 6% and 41% of patients with psoriasis (PsO) will be diagnosed with PsA in their lifetime. 2 PsA has a heterogeneous presentation 1,2 with broad negative effects on physical, psychological, and social functioning leading to lower quality of life. 3 In addition, PsA has a high economic burden estimated to cost nearly $30,000 per patient each year. 4 Treatments for PsA are collectively known as diseasemodifying antirheumatic drugs (DMARDs), and treatment choice depends on severity of disease, treatment history, and presence of other comorbidities such as PsO. 5 Conventional DMARDs (cDMARDs) such as methotrexate and leflunomide can be recommended as the first line of treatment for patients without severe disease. 5 Advanced therapies, including biologic DMARDs (bDMARDs) and targeted synthetic DMARDs (tsDMARDs), are recommended for patients with inadequate response to cDMARDs or with more severe disease. 5 bDMARDs approved for treatment of PsA include tumor necrosis factor inhibitors (TNFis), interleukin (IL) 12/23, 23, and 17A inhibitors, and CTLA4-immunoglobulin, whereas tsDMARDs include Janus kinase inhibitors and phosphodiesterase 4 inhibitors. 5,6 Although these advanced therapies are effective for many patients, dose escalations, adjunctive use of pain and anti-inflammatory medications (eg, corticosteroids, nonsteroidal anti-inflammatory drugs [NSAIDs], and opioids), or switching between advanced therapies may be necessary to adequately control pain and inflammation. 7 Although PsA treatment guidelines include strategies for switching between DMARD therapies, they provide little guidance around adjunctive pain and anti-inflammatory medication use. 5,8 A multinational collaboration of 453 rheumatologists from 17 countries developed recommendations for the use of pharmacotherapy for pain management in patients with inflammatory arthritis, including PsA, based on systematic literature review and expert consensus. 8 Although the level of evidence supporting the recommendations was varied, this collaboration found evidence to support the use, when necessary, of paracetamol, NSAIDs, methotrexate (ie, cDMARDs), weak opioids (for short termtreatment when other therapies have failed), and tricyclic antidepressants or neuromodulators as adjuvant treatments. Systemic glucocorticoids were not recommended in the absence of signs and symptoms of inflammation, and strong opioids were suggested only for exceptional cases. 8 Much of the existing literature examining treatment patterns and adjunctive pain and anti-inflammatory medication use among patients with PsA predates the approval and uptake of IL-17A inhibitors. 7,9 There are currently 2 IL-17A inhibitors approved by the US Food and Drug Administration (FDA) for treatment of PsA: ixekizumab (Taltz; Eli Lilly and Company), approved in December 2017, and secukinumab (Cosentyx; Novartis AG), approved in January 2016. To better understand the real-world use of these targeted therapies, this study compared treatment patterns and use of pain and anti-inflammatory medications between patients with PsA initiating ixekizumab and secukinumab.

DATA SOURCE AND STUDY DESIGN
We conducted a retrospective cohort study using longitudinal claims within the HealthCore Integrated Research Database (HIRD). The HIRD includes medical and pharmacy administrative claims data from 14 geographically diverse states in the United States. 10 Patient enrollment data, inpatient and outpatient medical care, and outpatient prescription drug use are tracked longitudinally for each patient. Researchers accessed a limited dataset for which data use agreements were in place with the covered entities in compliance with the Health Insurance Portability and Accountability Privacy Rule, and therefore, institutional review board approval was not required.

STUDY POPULATION
The study population included adult patients with commercial or Medicare Advantage/Supplemental & Part D standardized difference [std diff] = −0.30), specialty of the index prescriber (std diff = 0.38), and mean number of prior advanced therapies (2.0 vs 1.5; std diff = −0.33) were different between cohorts. Cohorts were well balanced after weighting. The majority of secukinumab patients (71%) received an index dose of 300 mg. Rates of persistence (ixekizumab: 40% vs secukinumab: 43%; P = 0.411) and switching (25% vs 20%; P = 0.072) were not statistically different between cohorts. Use of new adjunctive pain and anti-inflammatory medications was not statistically different between cohorts either (ixekizumab: 63% vs secukinumab: 58%; P = 0.187).

CONCLUSIONS:
Real-world treatment patterns and use of adjunctive pain and anti-inflammatory medications were similar in patients with PsA initiating ixekizumab and secukinumab in this US-managed care population. Further research examining reasons for discontinuation, switching, and use of adjunctive medications may help inform treatment decisions for patients living with PsA. treatment regimens during the first 84 days: (1) 80 mg every 4 weeks (Q4W), (2) 80 mg every 2 weeks (Q2W; dosing regimen indicative of moderate to severe PsO), or (3) other. Based on the US secukinumab label, patients initiating secukinumab were classified into 4 possible dosing regimens during the first 28 days after the index date: (1) 150 mg Q4W, (2) 150 mg every week (QW), (3) 300 mg QW (dosing regimen indicative of moderate to severe PsO), and (4) other. As secukinumab has 2 dosing options, 150 mg or 300 mg, dose changes were assessed after the first 28 days following the index date. Patients were classified as increasing from 150 mg to 300 mg, decreasing from 300 mg to 150 mg, or as having no dose change during the remainder of the 12-month post-index period. For patients with multiple dose changes, only the first dose change was recorded.
Treatment patterns were assessed over the 12-month post-index period. Adherence to the index medication was measured as proportion of days covered (PDC), calculated as the number of days with drug on-hand divided by the number of days in the post-index period (ie, 365 days). PDC was adjusted for overlapping days supply assuming patients who refilled early would not begin the new medication until the end of the preceding medication's days supply. Patients with PDC of 0.8 or more were classified as adherent. Persistence to the index medication was measured as the number of days of continuous therapy from the point of treatment initiation to the end of the post-index period, allowing for a maximum fixed gap of 45 days between the run-out date of the previous fill (ie, fill date plus days supply) and the date of the subsequent fill. Discontinuation of the index medication was defined as the failure to refill the index medication within 45 days after the run-out date of the previous fill. The run-out date of the previous fill before the qualifying 45-day gap was recorded as the discontinuation date. Patients who discontinued were classified into 3 groups based on events until end of follow-up: (1) those who discontinued and restarted the index medication, (2) those who discontinued and switched to another advanced therapy, and (3) those who discontinued without restarting or switching. For patients who both restarted and switched to another advanced therapy, the first restart or switch was captured. A sensitivity analysis using a gap of 60 days was conducted to understand the impact of changing the gap on treatment patterns.
Among those persistent to the index medication for the first 90-days post-index (the onboarding period), use of new pain or anti-inflammatory medications was assessed. New use of pain or anti-inflammatory medications was assessed overall and by medication class. The following were considered unique classes of pain or anti-inflammatory medications: cDMARDs, corticosteroids, health insurance coverage who had at least 1 fill for ixekizumab or secukinumab during the patient selection period (December 1, 2017, to November 30, 2019), which aligns to the FDA approval date of ixekizumab in December 2017. The earliest fill was set as the index date and determined the cohort. Patients could not have claims for the other cohort drug (eg, ixekizumab cohort could not have claims for secukinumab) in the 6 months prior to and including the index date (baseline period). Furthermore, to identify new users, patients could not have claims for their index drug in the baseline period (eg, ixekizumab cohort could not have claims for ixekizumab). Patients had at least 2 claims with PsA diagnoses occurring at least 30 days apart during the study period (June 1, 2017, to November 30, 2020), 1 of which had to occur within the baseline period, and no claims for ankylosing spondylitis or nonradiographic axial spondylarthritis during the baseline period. Patients with enthesitis-related arthritis were not excluded as secukinumab was approved for this condition in December 2021 after the study period ended. Patients were required to have continuous pharmacy and medical benefit enrollment in the baseline period and for at least 1 year after index date. See Supplementary  Table 1 (available in online article) for diagnosis codes and Supplementary Figure 1 for the study design diagram.

STUDY MEASURES
Patient demographics and prescribing provider specialty were assessed on the index date. The Quan-Charlson Comorbidity Index (QCI) score and other comorbidities were assessed during the baseline period (see Supplementary  Table 1 for diagnosis codes). 11 Pain and anti-inflammatory medication use was assessed during the baseline period and included cDMARDs, corticosteroids, neuromodulators, NSAIDs, opioids, and topical pain medications (Supplementary Table 2). Pre-index advanced therapy use was assessed in the all-available continuous pre-index enrollment period, which was captured as the start date of health plan enrollment to 1 day prior to index date (variable for each patient). Pre-index advanced therapy use was captured as any use and as the count of unique medications used. Additionally, the count of unique TNFi biologics, non-TNFi biologics, and other advanced therapies was recorded.
For a summary of ixekizumab and secukinumab dosing schedules listed on the US label, please see Supplementary  Table 3. Because ixekizumab is dispensed in 80 mg strength formulations, patients were classified as having the 160 mg initial dose if the quantity dispensed for ixekizumab on the index date was 2 or more. Next, patients initiating ixekizumab who were persistent for the first 84 days (ie, treatment initiation period for patients with comorbid moderate to severe PsO) were classified into 3 possible   TABLE 1 continued on next page governed, whereas ixekizumab often required failure of 2 preferred drugs before it could be authorized. 12 To account for potential confounding, such as differences in preferred drug status, demographics, or comorbidities, propensity scores (PSs) (ie, the probability of initiating ixekizumab vs secukinumab) were calculated by logistic regression and transformed into weights for adjusted inverse probability of treatment weighting (IPTW) analysis. 13 IPTW was selected over PS matching given the limited sample size for ixekizumab. IPTW allows for retainment of the full sample to be used for analysis. Weights were chosen to estimate the average treatment effect on the treated (ATT) (ie, ixekizumab patients). Baseline demographics, clinical characteristics, health care resource utilization, and prior advanced therapy use were considered for inclusion in the PS model, which was based on prior studies comparing ixekizumab and secukinumab among patients with PsO. 14,15 Additionally, as use of pain and anti-inflammatory medications was an outcome of interest, baseline use of these medications was considered for inclusion in the PS neuromodulators, NSAIDs, opioids, and topical pain medications (Supplementary Table 2). A pain or anti-inflammatory medication was considered new if the patient had at least 1 medical or pharmacy claim for it between 91 days after index date and the end of follow-up (add-on period) and had no claims for it in the onboarding period. 7,9 A 90-day cutoff was chosen as the onboarding period because ixekizumab and secukinumab are expected to reach maximum efficacy 90 days after initiation. 9

STATISTICAL ANALYSIS
In this real-world observational study, the causal relationship between treatment assignment (ixekizumab vs secukinumab) and outcomes of interest (treatment patterns and pain/anti-inflammatory medication use) may be confounded by the absence of random cohort assignment. For example, during the study time frame, secukinumab was a preferred PsA drug under the health plan formulary by which the claims adjudication for the HIRD is  TABLE 1 balanced. 13 Multiple weights were generated: 1 for the full sample, which was used to assess treatment patterns, and 1 for patients who were persistent to the index medication during the onboarding period, which was used to assess use of new pain or anti-inflammatory medications.
model. The performance of the weighting procedure was examined by comparing key baseline variables of interest using standardized differences (std diffs) before and after weighting with IPTW. A standardized difference threshold of 10% or less between cohorts was considered adequately

TABLE 2
diff = 0.10) than secukinumab patients. Additionally, the cohorts differed based on geographic region of residence before weighting (std diff = 0.15). Cohorts had similar QCI scores (std diff = 0.02) and similar rates of comorbidities apart from PsO (60% vs 45%; std diff = −0.30) and dyslipidemia (36% vs 29%; std diff = −0.15), which were both higher among ixekizumab patients. Additionally, a higher proportion of ixekizumab patients had their index claim prescribed by a dermatologist (28% vs 14%), whereas a lower proportion had their index claim prescribed by a rheumatologist (52% vs 68%; std diff = 0.38). Baseline use of pain and anti-inflammatory medications was mostly similar between cohorts; a lower proportion of ixekizumab patients used corticosteroids (46% vs 51%; std diff = 0.11) in the baseline. Although a similar proportion of patients in both cohorts had ever used an advanced therapy (ixekizumab: 86% vs secukinumab: 86%; std diff < 0.01), ixekizumab patients had used more unique advanced therapies pre-index than secukinumab patients (2.0 vs 1.5; std diff = −0.33). After weighting, all baseline demographic and clinical characteristics were well balanced, except for the count of prior advanced therapies used, which remained Descriptive statistics including means and SDs for continuous variables and frequencies and percentages for categorical variables were calculated. Chi-square and Fisher's exact tests for categorical variables and unpaired t-tests for continuous variables were used to compare weighted outcomes across cohorts. A robust variance estimator was used to compare weighted outcomes postindex to account for lack of independence in replications of subjects introduced by weighting. Instant Health Data software and SAS Enterprise Guide 8.3 were used to conduct all analyses. A threshold of P < 0.05 was used to define statistical significance, and no adjustments were made for multiple testing.

DEMOGRAPHICS AND BASELINE CHARACTERISTICS
In total, 407 patients in the ixekizumab cohort and 1,508 patients in the secukinumab cohort met selection criteria (Supplementary Table 4). Before weighting, ixekizumab patients were older (51.6 vs 50.1 years; std diff = −0.14) and had a lower proportion of females (54% vs 59%; std

TREATMENT PATTERNS
In the post-index period, the mean PDC was not significantly different between cohorts (ixekizumab = 0.58 vs secukinumab = 0.61; P = 0.078). Additionally, when comparing ixekizumab with secukinumab, mean days of persistent use (219.6 days vs 231.9 days; P = 0.322) and the proportion of patients persistent at the end of the post-index period (40% vs 43%; P = 0.411) were not significantly different between cohorts. The proportions of patients who discontinued and restarted their index medication (20% vs 22%; P = 0.513), discontinued and switched to a different advanced therapy (25% vs 20%; P = 0.072), and discontinued without a restart or switch (14.7% vs 15.3%; P = 0.823) were not significantly different between cohorts (Table 3; Figure 1). In the sensitivity analysis that used a 60-day gap to define persistence, the larger gap did not affect comparative outcomes of treatment patterns.

USE OF NEW PAIN AND ANTI-INFLAMMATORY MEDICATIONS
In total, 86.7% (353/407) of ixekizumab patients and 86.7% (1,308/1,508) of secukinumab patients were persistent to the index medication at the end of the onboarding period. This cohort was similar to the full cohort with a few exceptions. First, there were fewer ixekizumab patients with commercial health coverage than secukinumab patients (94% vs 97%; std diff = 0.11). Additionally, more ixekizumab patients had comorbid hypertension than secukinumab patients (43% vs 37%; std diff = 0.13). Finally, a lower proportion of ixekizumab patients had baseline NSAID use than secukinumab patients (37% vs 42%; std diff = −0.11). After weighting, cohorts were well balanced (Supplementary Table 5).
In the add-on period (day 91 to day 365), use of any new pain or anti-inflammatory medication was not significantly different between cohorts (ixekizumab = 63% vs secukinumab = 58%; P = 0.187), and there were no significant differences by medication type. Additionally, mean days to first new use of a pain or anti-inflammatory medication was not significantly different (ixekizumab = 147.2 days vs secukinumab = 145.6 days; P = 0.804) ( Table 4).

Discussion
To our knowledge, this is among the first studies comparing real-world treatment patterns of ixekizumab with those of secukinumab among patients with PsA. In this retrospective study in a US-managed care population, ixekizumab patients had more baseline comorbid PsO and used more advanced therapies pre-index than secukinumab patients. After adjusting for these differences using IPTW, post-index marginally imbalanced with ixekizumab patients using more advanced therapies (std diff = 0.11) ( Table 1).

DOSING
Among secukinumab patients, 71% received an index dose of 300 mg. In the first 28 days of treatment, 49% of secukinumab patients received 300 mg QW, 21% received 150 mg QW, 8% received 150 mg Q4W, and 22% received a different regimen. Among those who began on 150 mg (n = 117), 48% increased to 300 mg in the post-index period, whereas 4% of those beginning on 300 mg (n = 278) decreased their dose to 150 mg.
Among ixekizumab patients, 75% received the index dose of 160 mg. In the first 84 days post-index, 50% of ixekizumab patients received 80 mg Q4W, 41% received 80 mg Q2W, and 9% received a different regimen. In both cohorts, less than 50% of patients had a dosing schedule consistent with the FDA-recommended dosing for moderate to severe PsO (41% vs 49%; P = 0.031) ( Table 2; Supplementary Table 3).  medical chart review study. 18 Prior research shows those on a 300 mg dose achieve a higher American College of Rheumatology Response 20 score at week 24 after treatment initiation than those on a 150 mg dose, especially among TNFi-experienced patients. [20][21][22] In our study, nearly 70% of secukinumab patients (weighted) were TNFi experienced, which may be driving preference for the 300 mg dose option among prescribers. Second, after weighting, comorbid PsO was documented in nearly 60% of patients in our study; however, less than 50% of patients in both cohorts had dosing regimens indicative of moderate to severe PsO. Previous studies have similarly found secukinumab dosing to be inconsistent with FDA-recommended dosing for moderate to severe PsO, 18,23 whereas a separate study found dosing for ixekizumab patients to be consistent with the label's dosing recommendations. 17 Our results in combination with prior studies show that the rationale for the initial dosing regimen may not always be driven by PsO severity (contrary to FDA recommendations) and/or comorbid PsO capture in claims data may be incomplete. The prevalence of pre-index advanced therapy use in the present study was high, with more than 85% of patients in both cohorts having used at least 1 advanced therapy. Importantly, many prior studies examining treatment patterns among patients with PsA limited cohorts to biologically naive patients, which is an important consideration when comparing with our study. 7,9,24 Nevertheless, a recent study examining treatment patterns among patients with PsA initiating ixekizumab found that more than 90% treatment patterns and use of new pain and anti-inflammatory medications were not significantly different between ixekizumab and secukinumab patients.
The higher prevalence of comorbid PsO prior to weighting among ixekizumab patients may be attributed to the FDA approval dates for PsA. Secukinumab was FDA approved for the treatment of PsO in January 2015 and for PsA in January 2016, whereas ixekizumab was approved for PsO in March 2016 and for PsA in December 2017. As the study period start aligned to the FDA approval date for ixekizumab in PsA, it is possible that uptake of the medication for PsA was slow and initially prescribed for patients with comorbid PsO, which had been approved for more than a year. Additionally, the higher prevalence of PsO, a skin condition, among ixekizumab patients may be driven by the higher prevalence of prescribing by dermatologists as they may be more likely to use the diagnosis code for PsO than rheumatologists. High prevalence of comorbid PsO among patients initiating IL-17A or IL-12/23 inhibitors has been consistently shown in the literature. [16][17][18] This aligns to treatment guidelines, which recommend the use of IL-17A or IL-12/23 inhibitors over other advanced therapies in patients with severe PsO. 5 Indeed, a recent study found that the presence of comorbid PsO was positively associated with the selection of an IL-17A or IL-12/23 inhibitor as the first line of therapy among patients with PsA. 19 There were several interesting findings from the dosing analysis. First, the majority of secukinumab patients initiated treatment on a 300 mg dose, a finding mirrored in a  improve patient experiences and outcomes while on these medications. Although the current study did not expand on this further, reasons for discontinuation may include loss of efficacy, disease progression, intolerance to or adverse events from the treatment, worsening or new comorbid conditions, and cost. 18 In the current study, approximately 60% of patients in both cohorts initiated a new pain or anti-inflammatory medication post-index. Our findings are higher than what was reported in 2 previous studies predating the approval and uptake of IL-17A inhibitors; however, these prior studies were among biologically naive patients. 7,9 Similar to these studies, however, use of corticosteroids, opioids, and NSAIDs were the 3 most common adjunctive medications used, suggesting a residual need in some patients for additional medications to control symptoms of PsA. 7,9 Importantly, our study showed that there was no significant difference in the use of new pain or anti-inflammatory medications between the 2 cohorts.

LIMITATIONS
These findings should be interpreted with consideration of several limitations. First, administrative claims are collected for the purposes of payment and may not reflect true diagnoses and treatment as coding issues may occur and medications may not be taken as prescribed. Second, certain characteristics such as preferences of the prescriber and health plan benefit design are not available in the claims data, and unmeasured confounding from these variables is possible. Third, certain medications (eg, tricyclic antidepressants) have multiple indications, and we are unable to discern for which indication these were prescribed. Fourth, some follow-up time overlapped with the beginning of the COVID-19 pandemic, which may impact results. However, the proportion of affected patients was similar in both cohorts (approximately 42% after weighting), so the relative comparisons are not likely affected. Fifth, over-the-counter use of pain medications was not captured. Finally, the study results may not be generalizable to the overall population because commercially insured patients may have different characteristics than those with public or no health insurance.

Conclusions
This study is among the first to compare real-world treatment patterns and use of pain and anti-inflammatory medications between patients with PsA initiating ixekizumab vs secukinumab. After adjusting for baseline differences, we found ixekizumab and secukinumab patients had similar treatment patterns (persistence, discontinuation, used a prior advanced therapy, and the average number of therapies used was 1.4. 17 Our study found the average number of pre-index advanced therapies prior to weighting to be 2.0 for ixekizumab and 1.5 for secukinumab patients. Use of more advanced therapies pre-index among ixekizumab patients is likely driven by the formulary of the health plan that governs adjudication of claims in the HIRD where secukinumab was a preferred biologic at the time of the study. 12 More than 80% of patients in both cohorts used pain and anti-inflammatory medications in the baseline period. Specifically, approximately 30% used cDMARDs, 40% used NSAIDs, and 30% used opioids in both cohorts. A recent study showed similar levels of baseline therapy among a mixed cohort of ixekizumab and secukinumab users with 27%, 34%, and 40% of patients using cDMARDs, NSAIDs, and opioids, respectively, at baseline. 25 Other studies, despite using a longer baseline period, found similarly high rates of baseline usage of pain and anti-inflammatory medications. 7,16,17,26,27 In the present study, 40% of ixekizumab and 43% of secukinumab patients were persistent in the post-index period, with 25% and 20%, respectively, switching to a different advanced therapy after discontinuation. A previous study predating the approval and uptake of IL-17A inhibitors for PsA found 45% of biologically naive patients were persistent to their index biologic and 23% switched to a different biologic after discontinuation, 7 whereas a second study found rates of persistence among biologically naive patients initiating IL-17A inhibitors to be 48%. 26 Another study using a cohort of biologically naive patients initiating non-TNFi biologics found that 18% of patients switched therapies after 12 months. 28 Differing rates of persistence and switching may be in part due to different definitions (eg, 45-day gap in our study vs 90-day gap in other studies), but may also be due to the high proportion of patients in our study who used prior advanced therapies, a potential marker of longer disease history or severity. One study that included biologically experienced patients found that 53% of ixekizumab initiators were persistent after 1 year of follow-up (using a 60-day gap) and 21% of patients switched to another advanced therapy. 17 Another study that included biologically experienced patients found that 64% of secukinumab initiators were persistent (using a 90-day gap), 27 whereas a separate study found that 56% of secukinumab initiators were persistent (using a 60-day gap) and 14% switched medications. 23 The use of different gaps to define discontinuation may in part explain the higher levels of persistence seen in these studies. High rates of discontinuation and switching (and low rates of adherence, as was also observed) suggest there may be ways to further switching, and adherence) and use of adjunctive pain and anti-inflammatory medications. Further research examining reasons for discontinuation and use of adjunctive therapies as well as research comparing treatment patterns by medications may inform treatment decisions for patients living with PsA.

DISCLOSURES
Ms Pizzicato, Ms Ketkar, and Dr Grabner are employees of HealthCore, Inc, which received funding from Eli Lilly and Company for the conduct of the study on which this manuscript is based. Ms Pepe was an employee of HealthCore, Inc., during the time the study was conducted. Dr Grabner is a shareholder of Elevance Health (legacy Anthem, Inc.). Dr Vadhariya, Dr Birt, and Ms Bolce are employees of Eli Lilly and Company, the manufacturer of ixekizumab (Taltz). Dr Birt and Ms Bolce are shareholders of Eli Lilly and Company. Dr Walsh is a paid consultant to Eli Lilly and Company and Novartis, the manufacturers of ixekizumab (Taltz) and secukinumab (Cosentyx), respectively. Additionally, Dr Walsh is a paid consultant for Pfizer, Janssen, AbbVie, and UCB and has contracts with Pfizer, AbbVie, and Merck.